The common denominator of patients with the acquired immune deficiency syndrome (AIDS) appears to be a broad spectrum of cellular immune dysfunction. Previous work in our laboratory has clearly demonstrated that macrophages of the reticuloendothelial system are defective in vivo, and preliminary evidence demonstrates that peripheral monocytes are also functionally abnormal in terms of microbiocidal activity, chemotaxis and phagocytic activity. However, we believe that these macrophage and RES defects are secondary to a more primary defect of T-helper lymphocytes. We have demonstrated that lymphocytes from AIDS patients are unresponsive to nonspecific and viral specific antigens in their ability to develop a lymphocyte blastogenic response and in the production of lymphokines (leukocyte inhibition factor or macrophage inhibition factor). Addition of interleukin-1 to antigen stimulated cultures enhanced lymphokine production in heterosexual controls and homosexual lymphadenopathy groups, but not in AIDS patients. Addition of IL-2 did not modulate lymphokine production in the control or AIDS patients. These data support the finding that IL-1 or IL-2 may be ineffective in the treatment of AIDS patients late in the disease but may have some immunomodulating effect earlier in the disease process as in lymphadenopathy patients. Work in this laboratory has now shifted focus onto the immunologic manifestations of AIDS in Zaire. Preliminary studies from our laboratory demonstrated an annual case rate in Zaire greater than any other site in the world (17/100,000). Immunologic features of these patients were similar to that identified in the United States, but immunologic abnormalities were also present in 25% of control patients with parasitic infections without AIDS. These included elevated circulating immune complexes, decreased T helper cells, hypergammaglobulinemia and decreased blastogenic responses. These preliminary data have prompted a more indepth evaluation of the immunologic, clinical and epidemiologic features of AIDS in Zaire. Early data has confirmed the finding of a retrovirus (HTLV-III/LAV) in 95% of Zairian AIDS patients. The significance of this project is to further develop our understanding of the etiology and immunopathogenesis of AIDS in U.S. and in Zaire.